The long term goal of these studies is to determine at a molecular level the structural basis for the known physiological function and mode of action of transferrin. In carrying this out we will study the crystal structures of iron saturated hen ovotransferrin, apo ovotransferrin and of selected non-physiological complexes with cations other than iron and synergistic anions other than the natural bicarbonate anion. These goals require the following procedures which are now underway in our laboratory: (a) Improved crystallization procedures to get a higher yield of diffraction quality crystals. (b) Screening of heavy atom derivatives. (c) Collection of X-ray data and solution of heavy atom derivative positions. (d) Preparation and crystallization of other metal complexes of transferrin. (e) preparation and crystallization of apo-transferrin. We have distinguished five specific structural problems which our crystallographic and ancillary studies will either establish or help to clarify. The most basic of these is the structure of the metal and anion binding sites. Eventually we also hope to clarify the changes that occur upon ion binding. Thirdly, we wish to identify and characterize the recognition site for the cell receptor. Finally, we will elucidate the questions of evolution and architecture involving the possibility of structural homology within the protein and the structural role of the carbohydrate moieties.